The discovery in our laboratory that extracts of HSV-infected cells could catalyze the phosphorylation of BrdC whereas extracts of uninfected cells could not will be extended towards the goal of highly selective chemotherapy of systemic, ocular and cutaneous HSV infections. 5-halogenated analogs of deoxycytidine, in combination with H4U (a potent inhibitor of cytidine deaminase) should be readily permeable to cells, not undergo catabolism (they are not substrates for uridine and thymidine phosphorylase) and are essentially not toxic to uninfected cells since such cells lack the ability to phosphorylate these analogs. BrdC and IdC are highly inhibitory to HSV-1 and -2 infected cells. We will determine if cells infected by varicella-zoster virus, cytomegalovirus, pseudorabies virus, vaccinia virus, Epstein-Barr virus, Marek's disease virus and Lucke frog virus possess the HSV-induced kinase. With a new assay we developed, we will determine if unlabelled 5-methyl- and 5-trifluoromethyl-deoxycytidine are substrates for the enzyme. We will test cells obtained from patients with cervical carcinoma, nasopharyngeal carcinoma, infectious mononucleosis and Burkitt's lymphoma for this unique kinase activity. We will utilize an in vitro assay that measures collective properties of tissues and an autoradiographic assay using 3H-MedC or 3H-BrdC to detect the unique kinase in cell populations where the activity may reside in a minor fraction of 'influential' cells. Enzymological studies on the purified pyrimidine nucleoside kinase will enable us to determine the nature of this unique activity and will guide a chemotherapeutic approach to HSV diseases. BIBLIOGRAPHIC REFERENCES: M.J. Dobersen, M. Jerkofsky and S. Greer. Enzymatic Studies on the Basis for Selective Inhibition of Herpes Simplex Virus and Varicella-Zoster Virus by 5-Bromodeoxycytidine. Fed. Proc. 35: 1969, (1976) (Abstract). M.J. Dobersen, M. Jerkofsky and S. Greer. Enzymatic Studies on the Basis for Selective Inhibition of Herpes Simplex Virus and Varicella-Zoster Virus by 5-Bromo-deoxycytidine. Proceedings of the New York Academy of Sciences, Third Conference on Antiviral Substances, Februrary, 1976. (Abstract).